Chloride channels serve a wide variety of specific cellular functions and contribute to the normal function of i.a. skeletal and smooth muscle cells. Chloride channels are probably found in every cell, from bacteria to mammals. Their physiological tasks range from cell volume regulation to stabilization of the membrane potential, transepithelial or transcellular transport and acidification of intracellular organelles.
Likewise, The Ca2+-activated BK channels are present in many cells including most central and peripheral nerve cells, striated muscle cells, cardiac cells, smooth muscle cells of the airways, the vasculature, the gastrointestinal tract and bladder, in endo- and exocrine glands including pancreatic b-cells and in kidney tubules.
There is a continued strong need to provide compounds active as chloride channel blockers or BKCa channel modulators and with an optimized pharmacological profile. Furthermore, there is a strong need to find effective compounds without unwanted side effects associated with older compounds.
WO 2005/023237 and WO 2005/023238 (Poseidon Pharmaceuticals A/S) describe the use of ERG channel openers for the treatment of hyperexcitability-related neuronal diseases and cardiac arrhythmias. Among the compounds disclosed is 1-(3-trifluoromethyl-phenyl)-3-[2-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-4-(4′-N,N-dimethyl-carbamoyl)-biphenyl]-urea.